The present invention relates to a DNA segment encoding a long isoform of a mammalian D.sub.2 dopamine receptor having a sequence of 29 amino acids that is absent in the known isoform of this receptor.
Dopamine receptors belong to a large class of neurotransmitter and hormone receptors which are linked to their signal transduction pathways via guanine nucleotide binding regulatory (G) proteins. Pharmacological, biochemical and physiological criteria have been used to define two subcategories of dopamine receptors referred to as D.sub.1 and D.sub.2.sup.1. D.sub.1 receptors are associated with the activation of adenylyl cyclase activity.sup.2 and are coupled with the G.sub.s regulatory protein.sup.3. In contrast, activation of D.sub.2 receptors results in various responses including inhibition of adenylyl cyclase activity.sup.4, inhibition of phosphatidylinositol turnover.sup.5, increase in K.sup.+ channel activity.sup.6 and inhibition of Ca.sup.2+ mobilization.sup.7. The G protein(s) linking the D.sub.2 receptors to these responses have not been identified, although D.sub.2 receptors have been shown to both co-purify.sup.8,9 and functionally reconstitute.sup.10,11 with both "G.sub.i " and "G.sub.o " related proteins.sup.3. One means of achieving the diversity of second messenger pathways associated with D.sub.2 receptor activation would be the existence of multiple D.sub.2 receptor subtypes, each being coupled with a different G protein-linked response. Efforts towards elucidating D.sub.2 receptor diversity were recently advanced by the cloning of a cDNA encoding a rat D.sub.2 receptor.sup.12. This receptor exhibits considerable amino acid homology with other members of the G protein-coupled receptor super-family for which cDNAs and/or genes have been cloned.sup.12,13.